We intend to continue our studies on the biochemistry of action of cytochalasins. It is hoped to further identify the nature of acceptor macromolecules for these drugs in eukaryotes; to investigate the mechanism of the in vitro interaction of novel cytochalasins, especially affinity-labelling species, with presumed receptors composed of contractile and cytoskeletal cellular elements; to define the structure-activity relationship of drug congeners and derivatives; and to probe further into the newly found physiological response of gram-positive bacteria to cytochalasin A. These investigations will, therefore, require substantial quantities of starting materials, now produced by in-house fermentation improvements; will utilize potential site directed and/or high specific activity drug analogs, now available by semi-synthetic procedures; and will employ appropriate biological test systems. The latter will include extracts made from Ehrlich ascites tumor cells and from Physarum polycephalum. The bacteriostatic effects of CA, involving such responses as inhibition of transport and enzyme inductions, will also be explored with the microorganism arthrobacter sialophilus.